The present invention relates to automatic samplers for automatically sampling liquid samples to be introduced into analytical apparatuses that analyze liquid samples, such as liquid chromatographs.
In a liquid chromatograph, an automatic sampler is used in order to automatically select numerous samples to be introduced to columns. FIG. 3 is a schematic diagram showing the channel structure of a conventional automatic sampler used in a liquid chromatograph, as shown in Patent Reference 1.
In the automatic sampler 3, the injection valve (high-pressure valve) 4 is a rotary six-port, two-position channel switching valve having six ports 4a–4f. Through a switching operation, two adjacent ports are selectively connected. In other words, the combinations of the two-port connections indicated by the solid or broken lines in FIG. 3 can be switched. The low-pressure valve 5 is a rotary seven-port, six-position valve having seven ports 5a–5g. The common port 5g, which is connected to a measuring pump 6, can be coupled to any one of the other six ports 5a–5f, which accordingly couples two predetermined adjacent ports among ports 5a–5f. For example, when the common port 5g is coupled to port 5b, ports 5a and 5f are coupled, as indicated by solid lines in FIG. 3.
A column channel, which extends to column 2, is connected to port 4b of the injection valve 4, and a mobile phase channel, which is supplied with a mobile phase (solvent) by the liquid feeding unit 1, is connected to port 4c. A sample loop 7 is connected to port 4d, and also to port 4a via the needle 10 and the injection port 9. Ports 4e and 4f are connected to ports 5b and 5c of the low-pressure valve 5, respectively. A cleaning port 8 is connected to port 5a of the low-pressure valve 5, port 5e is connected to the measuring pump 6, and a cleaning solution is supplied to port 5d. A small vial 11 containing a liquid sample is stored in a sample rack 12. The needle 10 is moved in horizontal and vertical directions using a moving mechanism 13. The needle can be moved to locations above the vial 11 and the cleaning port 8, and inserted into the respective liquids contained therein.
The basic sequence of operations for introducing a liquid sample in the apparatus described above will be explained. When the liquid sample is collected, the injection valve 4 and the low-pressure valve 5 are switched to the connected state indicated by the solid lines in FIG. 3, and the needle 10 is moved to the location above the vial 11 and inserted into the liquid sample (the position indicated by reference numeral 10′). When the plunger of the measuring pump 6 is pulled in this state, the liquid sample is suctioned from the vial 11 through the mobile phase (or a cleaning solution made of the same components) that fills the connecting channel between the measuring pump 6 and the needle 10, and the liquid sample is held within the sample loop 7. The amount of the liquid sample collected is equivalent to the amount of suction developed by the measuring pump 6.
After the sample is collected, the needle 10 is returned to the position above the injection port 9 and connected to the injection port 9. The injection valve 4 is switched to the connected state indicated by the broken lines in FIG. 3. The mobile phase supplied from the liquid feeding unit 1 is transmitted to the column 2 via the sample loop 7, needle 10, and injection port 9. At this point, the liquid sample, which has been held within the sample loop 7, is fed to the column 2 along with the mobile phase. The liquid is separated into components as it passes through the column 2 to be sequentially detected by the detector, which is not shown.
The needle 10 on which the liquid sample is deposited during the suction is cleaned as follows. The injection valve 4 and the low-pressure valve 5 are switched to the connected state indicated by the solid lines in FIG. 4. The plunger of the measuring pump 6 is pulled to suction the cleaning solution into the syringe. When the injection valve 4 and the low-pressure valve 5 are subsequently switched to the connected state indicated by the broken lines in FIG. 3, and the plunger is pressed to eject the cleaning solution from the measuring pump 6, the cleaning solution is introduced to fill the cleaning port 8, while discharging excess cleaning solution from the discharge port of the cleaning port 8. The needle 10 is then moved to the location above the cleaning port 8, as shown in FIG. 4, and dipped into the cleaning solution contained in the cleaning port 8. Upon cleaning the needle 10 for a certain period of time, the needle is returned to the injection port 9.
In the aforementioned automatic sampler 3, since the cleaning of the needle 10 described above is always performed between the introductions of one liquid sample and the next, the likelihood of cross-contamination, wherein the previous sample is mixed into the following sample, is reduced. However, even with such cleaning steps, cross-contamination is not completely eliminated. One reason for that is explained below.
FIG. 5 is an enlarged schematic longitudinal sectional view of the section where the needle 10 comes in contact with the injection port 9. The section indicated as “A” of the needle 10 is straight, and the section indicated as “B” is tapered so that the outer diameter thereof is continuously reduced towards its tip. The sealing member 90 disposed in the injection port 9 is provided with an insertion hole 90b with a wider funnel section 90a. To connect the needle 10 to the injection port 9, the needle 10 is lowered so that the tip end of the needle 10 is inserted into the insertion hole 90b of the sealing member 90.
Since the inner diameter of the insertion hole 90b is larger than the outer diameter of the tip end of the needle 10, the tip end of the needle 10 begins entering the insertion hole 90b. Since the tip section of the needle 10 is tapered, the outer surface of the needle 10 comes in contact with the inner surface of the insertion hole 90b when the needle 10 is lowered to a certain position. The needle 10 is lowered by a predetermined level of pressure; the needle 10 is pushed in while the pressure overcomes the frictional force (including the resilience of the sealing member 90) of the contact surface, but the lowering of the needle 10 ceases once the frictional force surpasses the pressure. In other words, at this point, the outer surface of the needle 10 is in tight contact with the inner surface of the insertion hole 90b, thereby securing fluid-tightness.
When a liquid sample is suctioned from the vial 11, some of the liquid sample is deposited on the outer part of the tip end of the needle 10. The needle 10 is subsequently inserted into the sealing member 90 of the injection port 9 as above, and thus the liquid sample gets deposited on the section of the inner surface of the insertion hole 90b of the sealing member 90 where the outer surface of the tip of the needle 10 comes in contact. The liquid sample adhering to the contact surface is not removed even when the mobile phase is supplied from the needle 10 to the injection port 9, and thus remains even after the removal of the needle 10. When the needle 10 is inserted into the insertion hole 90b of the sealing member 90 in order to introduce the next liquid sample, the previous liquid sample adhering to the inner surface of the insertion hole 90b may be pushed by the needle 10 and mixed in the channel.
Such cross-contamination described above often causes problems, particularly in analyzing samples that are easily adsorbed by the surface of a needle 10 made of metal, such as basic compounds and lipid soluble substances.
Conventionally, for example, as in the automatic sampler disclosed in Patent Reference 2, a vapor-deposit or coating of precious metal is applied to the outer surface of the tip section of the needle in order to make the chemical adsorption of samples more difficult. Such a technique may be effective for samples that adhere to the needle surface mainly through chemical adsorption, such as basic compounds, but is not effective for samples that adhere to the needle surface through causes other than chemical adsorption, such as with lipid soluble substances.
Patent Reference 1: Japanese Laid-open Patent Publication No. 2002-277450
Patent Reference 2: Japanese Laid-open Patent Publication No. 2002-228668
In recent years, with increased levels of sensitivity and precision of analytical apparatuses, even a trace amount of cross-contamination such as that described above has begun to greatly affect the results of analyses. Moreover, samples that are subject to analysis have also diversified. A need exists for a cross-contamination reduction measure that does not depend on the type of samples.
An object of the present invention is to solve the aforementioned problems associated with conventional sampling devices. It is an object of the present invention, therefore, to provide an automatic sampler that enables high-sensitivity and high-precision analyses by significantly reducing the amount of cross-contamination, regardless of the type of samples.
While in the aforementioned conventional approach, the surface of a needle is designed so as to make adhesion of samples more difficult, the present invention addresses the fact that the amount of cross-contamination greatly depends on the contact area between the outer surface of the needle tip and the inner surface of the injection port's insertion hole. The present invention, therefore, is based on reducing the amount of cross-contamination by reducing the contact area.
Further objects and advantages of the invention will be apparent from the following description of the invention and the associated drawings.